1. UNIT THREE BIOLOGY AREA OF STUDY #1: MOLECULES OF LIFE EXAM REVISION LECTURE CHP 4: MOLECULAR BIOLOGY IN MEDICINE

2. CHP 4 TOPIC 1: HISTORY AND PURPOSE Purpose of Molecular Biology enhance knowledge of molecular biology understand a range of applications of molecular biology in medicine, including – designer drugs, diagnosis of genetic conditions before and after birth, production of hormones and plant vaccines. Molecular Biology in Medicine involves knowledge and manipulation of genetic material design and development of drugs to prevent the specific action of an infective micro-organism design and development of drugs to inhibit the action of specific chemicals in the body manufacture of compounds for use by people deficient in a vital chemical, such as a particular hormone development and delivery methods for efficient drug use

3. Discovery of the link between inheritance and the human condition, Aklaptonuria (as an inherited disease) in 1902. Sir Archibald E. Garrod related this condition to a lack of an enzyme Oswald Avery: “inherited material was DNA” in 1943 Watson & Crick – DNA structure discovery 1953 Today, the role of proteins, not just DNA is increasing in emphasis CHP 4 TOPIC 1: HISTORY AND PURPOSE

4. Example: PKU – Phenylketonuria Is an inherited disease Prevelance 1 in 10 000 Affected person fails to produce the enzyme phenylalanine hydroxylase Prior to 1960: untreated affected person unable to metabolise phenylalanine to tyrosine Build up of phenylalanine causes brain damage Testing: today – mass spectrometry Treatment: supply of diet free of phenylalanine – results in normal development CHP 4 TOPIC 1: HISTORY AND PURPOSE

5. Medical Treatments Gene Therapy Some genetic diseases can’t be treated by diet changes. Why not try to insert a normal functional gene into cells that contain a defect. Such a procedure is called gene therapy. Defn: Gene Therapy – A medical procedure that modifies the genetic material of living cells of an individual so that the gentic effect is corrected Two categories of Gene Therapy 1.in vivo gene therapy given directly to a patient 2.Ex vivo gene therapy (cells manipulated outside the body then re-inserted) – Functional piece of DNA called a cloned gene – often inserted with use of a vector, such as a virus: Retroviruses Adenoviruses CHP 4 TOPIC 2: MEDICAL TREATMENTS USING MOLECULAR BIOLOGY

7. Topic CHP4.1 Questions: 1.Which of the following are credited with discovering the structure of DNA: (circle) Oswald Avery/ Sir Archibald E Garrod/ Watson & Crick 2.The (base) cause of PKU is: (circle) nutritional/ genetic (i.e hereditary)/ environmental 3.A series of linked metabolic reactions is called a: _____________ ________________ Topic CHP4.2 Questions: 1.The manipulation of DNA to insert a preferred gen is known as: ____________________ 2.The two categories of Gene Therapy include: __________________, & _______________ 3.A functional piece of copied DNA is called: ______________DNA 4.Two vectors used to insert (copied) DNA into an individual include: ___________ & ___________ 5.Which macromolecule is also used as a vector for the insertion of DNA into cells: _______ /8 Marks

8. Medical Diagnosis – Prenatal Testing Genetic tests of unborns include: – Ultrasound – Chorionic villus sampling (CVS) – Amniocentesis – electrphoresis Genetic Tests after birth include: – Presymptomatic testing for; breast cancer & Huntington’s disease CHP 4 TOPIC 3: MEDICAL DIAGNOSIS USING MOLECULAR BIOLOGY

9. Medical Diagnosis Ultrasound: – Technique using sound waves to form an image of internal structures, including a fetus in its mothers uterus Chorionic villus sampling (CVS) – Prenatal process of obtaining a sample of chorion tissue that surrounds a developing embryo or early fetus and includes cells of embryonic or fetal origin Amniocentesis – Procedure in which a sample of amniotic fluid that surrounds a fetus in uterus (containing fetal cells) is obtained Electrophoresis – Technique for sorting out lengths of DNA fragments through an electric field Presymptomatic Tests – DNA-based technique for distinguishing whether a person is ‘at risk’ but who shows no clinical sign of a given genetic disease CHP 4 TOPIC 3: MEDICAL DIAGNOSIS USING MOLECULAR BIOLOGY

10. Ultrasound: Technique using sound waves to form an image of internal structures, including a fetus in its mothers uterus

11. Amniocentesis Procedure in which a sample of amniotic fluid that surrounds a fetus in uterus (containing fetal cells) is obtained Chorionic villus sampling (CVS) Prenatal process of obtaining a sample of chorion tissue that surrounds a developing embryo or early fetus and includes cells of embryonic or fetal origin

12. Electrophoresis Technique for sorting out lengths of DNA fragments through an electric field

13. Rational Drug Design essentially involves finding out how the infective agent works against a cell and using that information to design a drug that prevents the infective agent from being able to do what it does Example: Relenza – anti influenza drug Neuraminidase, protein on surface of the virus, allows exit of new virus particles from a cell Neuraminidase structure varies between virus strains Scientists found a common structural component, which was the active site Computer modelling of the active site was completed A drug to bind with the active site was then designed this technique, in which the active site of a molecule is determined and a second molecule (the drug) is constructed to fit into the active site to inhibit the activity of the first molecule, is called rational drug design CHP 4 TOPIC 4: RATIONAL DRUG DESIGN

14. Insulin Production role of insulin: hormone that controls uptake of glucose DNA sequence coding for insulin (a protein) production well known Sequence of DNA can be constructed and inserted into a plasmid vector Plasmid inserted into bacteria where they replicate Bacteria become insulin factories, secreting insulin Insulin is isolated, purified and packaged into vials for diabetics See figure 4.29 a&b Growth Hormone Production role of growth hormone: growth Normally produced by pituitary gland Gene can be copied through genetic engineering Factor VIII Production role of Factor VIII: involved in blood clotting (absence causes –haemophilia) Gene on X chromosome (much more common in males as it is recessive) Factor VIII produced by similar methods to insulin and growth hormone CHP 4 TOPIC 5: MANUFACTURING BIOLOGICAL MOLECULES

16. Topic CHP4.3 Questions: 1.(Fill in the gaps) 2.______________________ is a procedure in which a sample of amniotic fluid (containing fetal cells) is obtained. 3.______________________ is a prenatal process wherby a sample of the chorion tissue surrounding a developing fetus is obtained 4.The basis for ‘electrophoresis’ is that different versions of genes are of different lengths and that DNA is ____________________ charged 5.Presymptomatic tests occur before/ after an at risk person shows signs of a disease Topic CHP4.4 Questions: 1.What is rational drug design? Topic CHP4.5 Questions: 1.With insulin production, the DNA clone is inserted into what?___________ 2.What name is given to enzymes that ‘cut’ DNA: ________________ 3.What name is given to ensymes that ‘stick’ DNA together? ________________

17. Drug Delivery By Plants The delivery of vaccines in plant material, as food, is currently being investigated. To develop such vaccines: – the molecular structures of proteins in the infective agent that cause the immune response are determined – the DNA that codes for some of these proteins is introduced into the plant genome – the plants are grown and harvested Example: Japanese research team developed rice that can deliver a cholera vaccine by genetically altering it to include DNA that codes for part of the protein of a cholera bacterium (thus initiating an immune response!) CHP 4 TOPIC 6: DRUG DELIVERY

18. Drug Delivery By Nanoparticles are manufactured through nanotechnology 1-100 nanometres in diameter, small enough to pass through a cell membrane made of a double layer of phospholipids so that they mimic the plasma membrane are used to deliver toxic drugs directly to target cells (such as tumour cells) reducing the chance of affecting healthy cells three compounds are attached to a dendrimer to be used in cancer treatment: – The drug methotrexate (to kill the cancer) – Five molecules of folic acid, a vitamin (attractive to cancer cells!) – A fluorescent stain (allows assessment and monitoring of the process) CHP 4 TOPIC 6: DRUG DELIVERY

19. Topic CHP4.6 Questions: 1.List the three steps involved with ‘drug delivery by plants” – __________________________________________________________ 2.How many nanometres in: 1 mm______________ 1micron:______________ 3.Why are nonparticles for drug delivery encased in phospholipid bilayer? __________________________________________________________ 4.What is the name given to the nanoparticle used for drug delivery:___________________ 5.Why is folic acid added to the nanoparticle identified above? ___________________________________________________________________